Glucocorticoid-induced osteoporosis is a severe side effect of long-term glucocorticoid therapy and the most common form of secondary osteoporosis. The molecular mechanisms underlying the deleterious effects of glu-cocorticoids in bone are complex. Glucocorti-coids exert several physiological metabolic actions including the regulation of glucose homeostasis and lipid metabolism and play a pivotal role in the regulation of inflammatory processes as well as in the maintenance of cir-cadian rhythms and regulation of acute and chronic stress. They have multiple effects on fetal development and in physiological concentrations, they are necessary for bone accrual and growth. Nevertheless, supraphysi-ological concentrations of glucocorticoids, either as part of the treatment of chronic inflammatory medical conditions or as a result of Cushing's syndrome negatively affect the bone. They enhance the activity of the bone-resorbing osteoclasts through the up-regu-lation of M-CSF und RANKL and concomitant down-regulation of OPG and activate inhibitors of the Wnt-signaling pathway such as sclerostin, thereby thwarting bone formation. Their direct inhibitory actions on bone-forming osteoblasts and osteocytes are considered pivotal for the pathogenesis of glucocorticoid-induced osteoporosis. Supra-physiological glucocorticoid concentrations block osteoblast differentiation and proliferation, activate pro-apoptotic signaling pathways in osteoblasts and osteocytes and hamper the mineralization process. Currently, therapeutic options to treat patients with glucocorticoid-induced osteoporosis are anti-resorptive and osteoanabolic drugs. The rationale of an early-on treatment with anti-resorptive drugs is based on the fact that glu-cocorticoids lead to an initial phase of accentuated bone resorption. Thus, clinical studies have proven that bisphosphonates are effective at reducing the occurrence of fractures in patients with glucocorticoid-induced osteoporosis. On the other hand, the inhibitory actions of glucocorticoids on bone formation render osteoanabolic drugs very attractive therapeutic options. The intermittent therapy with teriparatide leads to a significant improvement of bone architecture and strength parameters as well as to a reduction of vertebral fractures and should thus be implemented especially by patients with severe forms of glucocorticoid-induced osteoporosis. Novel osteoanabolic agents such as ro-mosozumab, a monoclonal antibody against sclerostin are currently being evaluated in clinical studies.